JPC SYSTEMIC PATHOLOGY
Signalment (JPC #2630322): Old military working dog
HISTORY: This dog had a mass on the right atrium of the heart.
HISTOPATHOLOGIC DESCRIPTION: Heart, right atrium: Expanding the myocardium and replacing 95% of cardiac myocytes, is an unencapsulated, poorly circumscribed, poorly demarcated, moderately cellular, infiltrative neoplasm composed of spindle cells forming irregularly sized blood-filled vascular channels, often wrapping collagen or rarely forming streams, bundles or more solidly cellular areas. Neoplastic cells have variably distinct cell borders, moderate amount of eosinophilic fibrillar cytoplasm, irregularly oval to elongate nuclei that occasionally bulge into vascular channels, coarsely clumped chromatin and up to 2 distinct nucleoli. Mitosis averages 3-5 per 40 x high power field. Anisokaryosis and anisocytosis are marked. Subjacent cardiac myocytes are swollen and pale (degenerate) or shrunken and hypereosinophilic with pyknotic nuclei (necrotic).There are and few fibrin thrombi, scattered single cell necrosis, scattered aggregates of lymphocytes, plasma cells, hemosiderin-laden macrophages, and viable and degenerate neutrophils. Surrounding the neoplastic cells is abundant hemorrhage, large coalescing areas of bright eosinophilic polymerized fibrin admixed with small amounts of necrotic debris, hematoiden and low numbers of hemosiderin laden macrophages.
MORPHOLOGIC DIAGNOSIS: Heart, right atrium: Hemangiosarcoma, breed not specified, canine.
- Malignant neoplasm arising from endothelium that often presents as multicentric disease involving spleen, liver, right atrium/auricle and lungs of dogs
- Most common primary neoplasm of the heart in dogs
- German shepherds are most commonly affected with multicentric disease, although any large breed dog appears to be at increased risk
- Overt metastasis is present in greater than 80% of dogs at clinical presentation
- Mean age of occurrence ranges from 8 to13 years in dogs
- Skeletal version is aggressive with bone destruction and pathologic fracture
- Must from the telangiectatic osteosarcoma and aneurysm
- Must demonstrate features of malignancy in endothelial cells
- Cutaneous or subcutanous tumors not uncommon in dogs; these may be solitary or part of the multicentric disease; canine dermal hemangiosarcomas may be solar induced; lightly pigmented, sparsely haired breeds are at increased risk; must differentiate from hemangioma
- Occasionally as a primary, aggressive bone tumor; also may arise in skeletal muscle
- Controversy over whether multicentric hemangiosarcoma is of true multicentric origin or one primary tumor with metastasis
- Visceral hemangiosarcomas: Highly aggressive, poor prognosis
- Primary cutaneous hemangiosarcomas: Less aggressive, longer survival times
- Mutations of the C-terminal domain of PTEN (phosphatase and tensin homolog gene on chromosome 10) have been identified in naturally-occurring canine hemangiosarcomas
- Sphingosine-1-phosphate (S1P) is a key biolipid signaling molecule that regulates cell growth and survival; functions to maintain HSA cell viability and proliferation.
- Increasing numbers of growth factors are found to be over expressed, and may be a target for future therapy:
- CD 117 (C-Kit) and VEGF 3 are overexpressed in hemangiosarcoma
- Several signaling pathways are also under investigation as targets for future therapy:
- Sphingosine-1-phosphate (S1P/S1P1 signaling pathway)
TYPICAL CLINICAL FINDINGS:
- Signs of right heart failure (abdominal distension, jugular pulses) caused by cardiac tamponade
- Severe arrhythmias may cause syncope, ataxia, and cyanosis
- Rupture of atrial hemangiosarcoma can lead to fatal hemopericardium
TYPICAL GROSS FINDINGS:
- Dark red mass; may be fluctuant or cystic
- Blood runs freely from cut surface
- In the heart, occurs subepicardially in the wall of right atrium at entrance to the auricle near coronary groove or in the auricular appendage
- Most common sites (dogs): spleen, skin, right atrium, liver
- Most common sites (cats): spleen, intestine, subcutaneous tissues
- Splenic hemagiosarcoma: often hemorrhagic, making it difficult for identification
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Spindle to polygonal to ovoid neoplastic cells that usually form vascular channels, spaces, or small clefts somewhere in the tumor
- Pleomorphic, hyperchromatic nuclei that often bulge into the lumina of vascular channels (“hob-nail”)
- Frequent mitotic figures; hemorrhage and necrosis; collagen wrapping
- Large solid areas may be difficult to distinguish from poorly differentiated sarcomas
- Weibel-Palade bodies are present in neoplastic cells
ADDITIONAL DIAGNOSTIC TESTS:
- IHC for panel of endothelial markers: ERG, Factor VIII-related antigen (vonWillebrand factor), claudin-5, and CD31 (platelet-endothelial cell adhesion molecule/PECAM), and an angiogenic factor (VEGF-A or Ang-2), especially in poorly differentiated hemangiosarcomas
Gross masses in or near the heart:
- Aortic body tumor (chemodectoma): Arises in ectopic thyroid or parathyroid tissue; white, firm mass at the base of the heart
- Rhabdomyoma/rhabdomyosarcoma: Rare in all species; gray nodules that often project into cardiac chambers
- Malignant lymphoma: Most common metastatic tumor involving the heart; nodular or diffuse, white, fleshy mass that resembles deposits of fat
- Granular cell tumor/Granular cell myoblastoma: Described in right atrium of a dog, but is usually seen in brain, meninges, lung, tongue
- Pericardial mesothelioma
- Myxoma/Myxosarcoma Most common cardiac tumor in adult humans, rare in animals; multilobular, soft and gelatinous
- Chondrosarcoma: Arises from cartilaginous or like-tissue of cardiac skeleton
- Neurofibroma/Schwannoma: Seen in cattle as single or multiple white nodules
Histologic differential diagnosis for vascular proliferations:
- Hemangioma: Well circumscribed neoplasm, vascular spaces are lined by a single layer of uniform endothelial cells and are filled with erythrocytes; hematomas can arise within a hemangiosarcoma, and obscure the sarcoma both grossly and histologically, especially within the canine spleen; lymphoid hyperplasia has been shown to be associated with splenic hematoma but not in hemangiosarcoma.
- Vascular hamartoma: An improper proliferation of normal blood vessels; endothelial cells are surrounded by tunica media and tunica adventitia
- Kaposi-like vascular tumor: Well-circumscribed neoplasm with angular slit-like vascular spaces with few erythrocytes surrounded by large cavernous vascular spaces, lymphocytes, and a thick fibrous capsule (This tumor is named for its similar histologic appearance to the human Kaposi sarcoma and has NO association with human herpes virus 8 or immunosuppression)
- Lymphangiosarcoma: Vascular channels containing few erythrocytes
- Granular cell tumor/Granular cell myoblastoma: Spindle to polygonal with granular cytoplasm; S-100 +
Hemangiosarcoma in other species:
- Incidence of cutaneous involvement appears to be on the rise; the head (especially eyelids), distal limbs, and paws are most often affected
- Other primary locations: Liver, spleen, mesentery, and omentum
- Sheep: Report of hepatic hemangiosarcoma
- Horse: Uncommon; reported in lung, pleura, skeletal muscle, spleen, heart, kidney, brain
- Cow: Rare reports
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